Cerebrospinal Fluid Total Protein Reference Intervals Derived from 20 Years of Patient Data

McCudden, Christopher R.; Brooks, John; Figurado, Priya; Bourque, Pierre R.

doi:10.1373/clinchem.2017.278267

Cited by 62 publications

(83 citation statements)

References 11 publications

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“…While more than 85% of laboratories worldwide consider 0.45 g/L to be the upper CSF reference limit, lower or higher reference limits are occasionally utilized [33]. Several studies have shown that the widely used cutoff of 0.45 g/L is erroneously low [34,35]. Implementation of CSF values of 0.50 g/L for patients aged B 50 years and 0.60 g/L for those aged [ 50 years have been proposed as a better standard CSF reference value [36].…”

Section: Laboratory Pitfallsmentioning

confidence: 99%

The Misdiagnosis of CIDP: A Review

Allen

2020

Neurol Ther

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There is a growing realization that many patients are incorrectly diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), with at least half of patients that carry a diagnosis of CIDP in the USA possibly having a different explanation for their neuropathy or having no neuropathy at all. Many misdiagnosed patients go on to receive costly and potentially harmful treatments for a disease that they do not have, while at the same time missing an opportunity to treat their true ailment. The cost of misdiagnosis on patients and society is not trivial. Many factors contribute to misdiagnosis. Particular points of vulnerability include the evaluation of ''atypical'' CIDP, interpretation of equivocal nerve conduction studies, over-reliance on elevations in cerebrospinal fluid protein concentration in indeterminate ranges, and placing excessive diagnostic weight on subjective changes following the initiation of immunotherapy. In addition to heighted awareness of the challenges, adherence to CIDP diagnostic guidelines, utilization of objective metrics to document clinical change, and referrals to CIDP centers of excellence are strategies that may improve diagnostic accuracy.

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Section: Laboratory Pitfallsmentioning

confidence: 99%

The Misdiagnosis of CIDP: A Review

Allen

2020

Neurol Ther

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“…There is now ample evidence indicating that the URL for CSF‐TP should be partitioned by age and that the widely used 45 mg/dl upper limit is erroneously low . The adoption of 45 mg/dl as the URL was based on the publication in 1938 of a study that sampled a reference population of younger patients.…”

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confidence: 99%

“…There is now ample evidence indicating that the URL for CSF-TP should be partitioned by age and that the widely used 45 mg/dl upper limit is erroneously low. 9,11 The adoption of 45 mg/dl as the URL was based on the publication in 1938 12 of a study that sampled a reference population of younger patients. Moreover, recent laboratory studies and a systematic review of the literature support implementation of CSF URL values of 50 mg/dl for patients aged ≤50 years and 60 mg/dl for those aged >50 years.…”

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confidence: 99%

Updated cerebrospinal fluid total protein reference values improve chronic inflammatory demyelinating polyneuropathy diagnosis

2019

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Introduction Recent literature has concluded that cerebrospinal fluid total protein (CSF‐TP) upper reference limits (URL) should be higher than 45 mg/dl and stratified by age. Methods Data‐driven URLs were applied to the analysis of a cohort of patients with correctly and incorrectly diagnosed chronic inflammatory demyelinating polyneuropathy (CIDP). Descriptive statistics were calculated, and exploratory analyses were used to test the impact of different CSF‐TP URLs on sensitivity and specificity of CIDP diagnosis. Results The adoption of higher and age‐dependent CSF‐TP URLs reduced the sensitivity of CSF analysis slightly (from 95% to 84%‐86%); however, the overall CIDP detection rate was unchanged. Twelve of 36 (33%) false‐positive diagnoses occurred with CSF‐TP elevation as the sole supportive criteria. By applying updated CSF‐TP URLs, the specificity of CSF analysis increased from 39% to 57%‐64%. Discussion Implementation of data‐driven CSF‐TP URLs improves CIDP diagnostic specificity without compromising sensitivity, thereby lessening CIDP misdiagnosis. Muscle Nerve 60: 180–183, 2019

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“…The elevation of serum NSE caused by unidentified hemolysis will be considered as abnormal results, which may affect the clinical decision‐making. Inspiration from several studies that have attempted to derive reference values from patient samples, the alternative way is to re‐establish the NSE reference interval including these invisible hemolysis specimens.…”

Section: Introductionmentioning

confidence: 99%

Correction of serum NSE reference intervals includes the unidentified hemolysis sample: 1‐year data analysis from healthcare individuals

Xie

Zhang

et al. 2019

Clinical Laboratory Analysis

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Background Reference intervals (RIs) are important for interpretation of laboratory results. Neuron‐specific enolase (NSE) can be utilized to aid the diagnosis of various tumors. However, while red blood cells contain NSE αγ‐isozymes, unrecognized slight hemolysis will result in increasing of NSE levels in serum. The aim of this study was to correct the NSE RIs from healthcare individuals results which may have unidentified microhemolysis. Methods A total of 15 047 healthy individuals undergoing regular health care were recruited to redefine the NSE reference interval according to the CA28‐A3 document. Volunteers with NSE level between 16.3 ng/mL and the upper limit of new RIs were performed venipuncture for NSE retest. Simultaneously, serum free hemoglobin (fHb) was performed with o‐tolidine test. Results Reestablishment of NSE RIs is 0‐18.9 ng/mL, which is wider than 0‐16.3 ng/mL provided by the manufacturer. Seventy‐four volunteers with the NSE level between 16.3 and 18.9 ng/mL were performed venipuncture for NSE retest. The ratio of NSE level drop to normal is 85.1% (63/74) in the subsequent results; there are significant differences between the median NSE of two groups (18.15 vs 14.15 ng/mL). Subsequently, the fHb concentration of 22 healthy individuals from 74 individuals was measured; there are significant differences between the median fHb of two groups (58 vs 30 mg/L). Conclusions Some specimens with slightly elevated NSE may be attributed to the unrecognized slight hemolysis. The correction RIs may be expected to decrease the abnormal NSE results.

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Cerebrospinal Fluid Total Protein Reference Intervals Derived from 20 Years of Patient Data

Abstract: The age dependence of CSF-TP supports that age-partitioned reference intervals will be more accurate than a single cutoff, particularly in patients with advancing age.

Cited by 62 publications

References 11 publications

The Misdiagnosis of CIDP: A Review

The Misdiagnosis of CIDP: A Review

Updated cerebrospinal fluid total protein reference values improve chronic inflammatory demyelinating polyneuropathy diagnosis

Correction of serum NSE reference intervals includes the unidentified hemolysis sample: 1‐year data analysis from healthcare individuals

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